The problem of injecting certain medicaments which are normally in a solid state, necessitating their reconstitution in solution before use has confronted the medical arts for many years. The basic reason is that a great many of these medicaments are not very stable in solution or, in other words, do not have a very long shelf life and consequently they must be prepared just prior to use. Such physical mixing presents many problems in proportioning and maintaining complete sanitary conditions.
Many attempts have been made to solve this by constructing a syringe in which the mixture or solution is effected by the action of the syringe itself in which the ingredients are pre-packaged separately and the mixing effected within the syringe, the injection effected and the syringe then discarded. None of these have been completely successful because of their failure in one or more of their requirements for a successful syringe of this type as listed below. These requirements are as follows:
1. Both solid medicament and liquid solvent must be hermetically sealed and kept in a sterile condition until ready for injection.
2. It must provide for safe sealing of the material to prevent accidental mixture before time for use.
3. The integrity of the system should be preserved to prevent contamination of the material from outside sources, including the atmosphere during storing, mixing and injection.
4. The injection needle must be kept sterile until injection is effected.
5. The syringe must be compact and completely packaged in a single unit before use.
6. It must provide for adequate mixing and dissolving of the materials.
7. It must be simple and operable by medical personnel in a conventional manner.
8. It must be simple and economical to manufacture.
9. It must be rigid and capable of withstanding shipment and handling by personnel.
10. The combination of medicament, diluent, rubber and glass should not combine to cause a particulate matter problem.
11. Once activated the unit should provide drug stability and pharmacological potency at room temperatures for at least eight hours.
12. It should not be subject to accidental activation, contamination, malfunction or disassembly.
13. It should have product stability capable of going to two years.
14. It must not require abnormal storage condition or handling.
15. It must have all components pre-attached so that no assembly is required for use.
16. The need to remove any parts prior to use should be minimal.
17. It should be capable of adapting to existing manufacturing process, knowledge and skills, including filling equipment.
18. It should be functional with presently approved rubber compound formulations.
Some of the attempts to satisfy these requirements are represented by the closest prior art known to applicant as set forth below.
U.S. Pat. No. 3,678,931 to Cohen covers a syringe in which the liquid is in an upper movable chamber and the powder in a lower chamber with a rubber seal in between. Moving of the plunger in the upper chamber parts the seal and forces the liquid into the lower chamber where it mixes with the solid. Further movement of the plunger pushes the upper chamber into the lower chamber and against another seal which is pierced by a hollow needle positioned in the bottom of the lower chamber. A cap or cover over the exterior of the needle is removed and the injection proceeds. In this device the shield between the liquid and solid is not positive but depends on the friction engagement and the medicament therefore is not tightly sealed. The needle likewise is not hermetically sealed throughout the operation but is exposed during the mixing.
U.S. Pat. No. 3,108,591 to Kolbas teaches the location of the powder in the upper portion of the syringe and the liquid in the lower. A hollow needle with an aperture is positioned at the bottom of the lower chamber. The seal at the bottom of the upper chamber is pierced by a needle when the upper chamber is pushed down and the liquid enters the upper chamber through an aperture in the needle where it mixes. A piston in the upper chamber is then pushed down to effect the injection. In this device the cover is also over the needle and must be removed and used on the piston in the upper chamber. The aperture in the side of the needle through which the liquid enters does not provide a positive displacement of the liquid and hence is not reliable and subject to easy clogging. The needle itself is not also hermetically sealed throughout.
U.S. Pat. No. 4,014,330 to Genese teaches a construction whereby powder is in one compartment with a puncturable seal and movable plunger. The fluid is in a separate vial with a puncturable seal also attached to a slidable piercing member having a hollow piercing needle. Screwing the vial on to the piercing member punctures this seal and further movement punctures the seal on the powder compartment causing fluid to enter. The injection needle is manually attached to the syringe compartment and further movement of sliding piercing members effects injection. This construction requires manual assembly before use, is not completely sterile or hermetic and somewhat complicated and not essentially self-contained initially.
U.S. Pat. No. 3,330,281 to Visser teaches a syringe with a plunger, piston and fluid containing barrel positioned over a vial or container with powder placed therein covered by a hermetically sealed plug. The needle at the bottom of the barrel passes through the plug into the vial and the powder. A friction cap is installed on the end of the needle. Movement of the piston puts pressure on the liquid forcing the friction cap off and into the powder and permitting liquid to mix with powder on the vial. After mixing, the syringe is turned upside down, the plunger withdrawn and fluid enters the barrel ready for injection. The presence of the cap in the powder violates the integrity of the system by introducing foreign matter into the powder providing a chance for contamination and accidental removal of the cap would cause premature mixing and malfunctioning of the device.
U.S. Pat. No. 303,846 to Ogle. Powder compartment and liquid compartment held together by threaded section in rubber seal. Slotted membranes separate compartments which are made to communicate when thread is loosened. Membranes depend on friction to maintain separation and to hold pressure when plunger is advanced for injection. Not positive separation of materials. Unconventional operation.
U.S. Pat. No. 3,255,752 to Dick. Liquid in internal upper portion of plunger. Powder in lower portion of barrel. Separated by radial port in plunger sleeve held closed by friction of resilient material. Opened by action of plunger exerting pressure on plunger sleeve. Not positive separation. Subject to accidental mixing. Needle in bottom of barrel subject to clogging by powder.
U.S. Pat. No. 3,464,412 to Schwartz. Liquid inside hollow plunger having a piston on one end. Powder in lower section of housing or barrel. Piston has fluid passage therethrough. Housing has fluid bypass at upper interior. When piston is withdrawn to be opposite latter, liquid flows out of bottom plunger barrel and into powder. Needle then attached and syringe ready for use. Separation not positive. Subject to leakage and unintentional mixing. Needle not protected.
U.S. Pat. No. 3,993,647 to the applicant discloses a mixing chamber to which a syringe may be attached. The chamber of a mixer and syringe are distinct and separate compartments, and while this is operable, it does not satisfy the requirements of compactness and general reliability.
U.S. Pat. No. 4,185,628 to applicant discloses concentric inner and outer chambers communicating and a plunger in the inner chamber for reciprocating and mixing the materials of both chambers. The injection needle is inserted in the end of the outer chamber and communicates with the inner chamber and responds to the action of the plunger in the inner chamber. While this is a practicable device in many ways, it is rather complicated and costly to manufacture and does not represent conventional operation of injection syringes.
It is evident from a study of the above patents that they do not fulfill the requirements of a satisfactory syringe set forth above and explain the reason that there is none known to the applicant which has acquired any appreciable commercial success.